Male breast cancer (MBC) is a rare disease and, because of its rarity, its etiology is poorly understood. However, germ-line mutations in breast cancer susceptibility gene BRCA2 are known to predispose to MBC. 1 Male carriers of BRCA2 mutations have an 80-100 times high risk for the development of breast cancer than the general male population thus making BRCA2 the strongest presently known MBC linked gene. 2 In addition to BRCA2, germ-line mutations in BRCA1, CHEK2, AR and PTEN have also been linked to increased MBC risk, 1 thus further supporting the role of genetic predisposition in the development of MBC. However, only a proportion of MBC cases (4-40% depending on the population) can be explained by mutations in BRCA2 and these other susceptibility genes. 1,3 Defects in genes functionally linked to BRCA2 might account for additional MBC cases. One such candidate gene is DSS1 (also known as SHFM1 and SEM1). DSS1 (deleted in split hand/split foot) encodes a 70 amino acids long, structurally and functionally highly conserved protein. [4][5][6] The gene was originally linked with split hand/split foot malformation (SHFM) on chromosome 7q21.3-q22.1 4 , but no definitive evidence for its role in this syndrome has been found. 7 Instead, DSS1 has been shown to interact directly with BRCA2. 6 Interactions of BRCA2 and DSS1, or their orthologues in lower organisms, have been convincingly demonstrated at least in yeast, fungi and mammalian cells. 6,8,9 The physical binding between these 2 proteins occurs in the most conserved portions of both proteins. 6,8 Interestingly, some of the known cancer predisposing mutations in BRCA2 affect amino acids that mediate the interaction of DSS1 with BRCA2 and, essentially all BRCA2 in mammalian cells is associated with DSS1. 8,10 Most importantly, the strong physical interaction between DSS1 and BRCA2 seems to be crucial for the BRCA2 function in the repair of DNA double-strand breaks. 8 Repair of DNA double-strand breaks during the G1/S and S/ G2 phases of the mitotic cell cycle occurs through 2 main mechanisms, non-homologous end-joining and homologous recombination. [11][12][13] Of these, the homologous recombination is an error-free repair mechanism and its proper function is critical for maintaining the chromosomal integrity. 12 BRCA2 functions in homologous recombination together with RAD51 recombinase and colocalizes to the sites of DNA damage. 14,15 Interestingly, Yang et al. 8 demonstrated that the same 90-kDa BRCA2 domain that binds to DSS1 also binds to singlestranded DNA. The function of DSS1 in this interaction remained unclear but DSS1 may regulate the accessibility of the DNA binding sites on BRCA2. 8 This model raises both DSS1 and BRCA2 in critical role in homologous recombina-Grant sponsor: Academy of Finland; Grant numbers: 211171, 207003.